There are many circumstances in which it is necessary to determine the level of one or more analytes in the blood of an individual at a given point in time. Often, a low volume blood sample extracted from the individual is sufficient for obtaining the required information. Such low volume blood samples are especially suitable in conditions wherein it is necessary to obtain a blood sample from the individual frequently, such as in the case of diabetic patients. Several years ago, a ten year long diabetes care and complications trial (DCCT) showed that the preferred mode of treatment of insulin dependent diabetes (Type 1) was by frequent small-dose administrations of insulin to such patients and determining the glucose level after each such administration. To follow such a treatment, a diabetic patient is required to puncture his skin and obtain a drop of blood for the glucose test at least three times a day. Such a frequent and repetitive puncturing is painful and often results in infection and formation of hard scar tissue and as a result, many diabetic patients neglect to sufficiently test their glucose level.
In an attempt to minimize the harm or pain caused by various techniques routinely used for obtaining a body fluid, several minimally invasive or non-invasive methods for determining the concentration of a substance in the blood by obtaining and analyzing a body fluid have been developed in which a very small sample of body fluid is obtained. Guy and Rao(1) have shown a method for determining the concentration of an inorganic or organic substance in an individual by obtaining an interstitial fluid sample from the individual by a process called iontophoresis. In accordance with this method, an electric field is employed which causes migration of ions which carry with them non-charged molecules, e.g. glucose.
Another minimally invasive method for obtaining a body fluid is that of SpecRx, Inc. Norcross, Ga., USA. A minute and shallow round hole is created in the skin, extending just below the stratum corneum and a sample of interstitial fluid is collected through this hole. That fluid is then tested for its glucose content by one of the methods known in the art.
In such minimally invasive methods the concentration of the tested substance in the obtained interstitial fluid sample often does not correctly indicate the level of the same substance in the blood of the tested individual at the time in which the sample was obtained or shortly thereafter. This is mostly due to the fact that the concentration of the tested substance varies in different locations in the body and at different hours of the day, and therefore, the concentration of a certain analyte in a body fluid other than the blood itself may significantly differ from its concentration in the blood at the same time. Moreover, although the side effects of such minimally invasive methods are reduced in comparison to some conventional methods for obtaining a blood sample, they still often result in discomfort to the tested individual, and involve wounding of the skin, and in some cases even disruption of blood vessels.
Attempts to detect the correct glucose level in the blood by determining the level of glucose in fluids of body samples other than blood such as saliva, urine or tears were found to be non suitable since the concentration of the glucose in such fluids was shown to be variable and, more often than not, did not directly reflect the concentration of the glucose in the blood at the relevant point in time(2-6).
Hair has also been used to detect the existence of various substances in a tested individual. The detection of a certain substance in the hair, obtained from an individual, provides evidence and information on the existence of the same substance in the tested individual at a certain, unknown period of time, i.e. that the individual was exposed at some time or another to the substance. Methods based on analysis of hair have been used, for example, in forensic medicine to determine whether an individual has, some time in the past, been exposed to drugs, for determining ABO blood groupings(7) (e.g. as evidence in cases of sexual assaults(8) etc.
The percent of protein glycation (i.e. binding of glucose to protein) in hair specimens has also been used to obtain information on the tested individual from which the hair specimen was obtained. The growth rate of hair is relatively high and therefore it is possible to compare the level of glycated protein in the older part of the hair closer to the level of the glycated protein in the newer part of the hair (closer to the root). A higher level of glycated protein in the newer part of the hair may, in some cases, indicate the development of a certain condition in an individual e.g. to predict the possible onset of diabetes(9).
All the above methods provide general information which enables to determine whether a tested individual was ever exposed to a substance of interest. Such methods have not been used for determining the level of a desired substance in the blood of the tested individual at the time in which the hair was obtained.
It has been shown that some of the above mentioned body samples, including urine, saliva or hair roots contain red blood cells(10-12).